Poly(ADP-ribose) polymerase family member 14 promotes functional recovery after spinal cord injury through regulating

Ai-Hua Xu1, Yang Yang1, Yang Shao1

  • 1Department of Rehabilitation Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.

Insights

Poly(ADP-ribose)polymerase family member 14 (PARP14) plays a crucial role in spinal cord injury (SCI) recovery. Downregulating PARP14 worsens functional impairment by promoting pro-inflammatory microglia, while its presence aids recovery.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Poly(ADP-ribose)polymerase family member 14 (PARP14) is known to aid functional recovery after stroke.
  • The specific role of PARP14 in spinal cord injury (SCI) has not been previously elucidated.
  • Understanding PARP14's function in SCI is critical for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the role of PARP14 in the context of spinal cord injury.
  • To determine the effect of PARP14 modulation on functional recovery, neuronal apoptosis, neuroinflammation, and microglia polarization after SCI.
  • To explore the underlying molecular mechanisms involving the STAT1/6 pathway.

Main Methods:

  • Establishment of a T10 spinal cord contusion model in C57BL/6 mice.
  • Intra-lesional injection of PARP14 shRNA-carrying lentivirus to silence PARP14 expression.
  • In vitro induction of microglia M1 and M2 polarization using specific stimuli.
  • Analysis of PARP14 expression, neuronal apoptosis, neuroinflammation, and microglia polarization.

Main Results:

  • PARP14 expression was upregulated in the injured spinal cord.
  • PARP14 downregulation exacerbated functional deficits, increased neuronal apoptosis, and heightened neuroinflammation.
  • PARP14 knockdown promoted M1 microglia polarization (pro-inflammatory) via the STAT1 pathway, whereas PARP14 overexpression favored M2 polarization (anti-inflammatory) through the STAT6 pathway.

Conclusions:

  • PARP14 plays a protective role in spinal cord injury.
  • PARP14 regulates microglial polarization through the STAT1/6 signaling pathway.
  • Targeting PARP14 may represent a promising therapeutic approach for improving functional recovery after SCI.